Bradykinin ("BK") is generated under normal conditions in mammalia by the action of various plasma enzymes such as kallikrein on high molecular weight kininogens. It is widely distributed in mammals, as are its two receptor subtypes, B.sub.1 and B.sub.2. The actions of BK at the B.sub.1 receptor include mainly contraction of arterial and venous preparations, although it can cause relaxation of peripheral resistance vessels as well.
Many of the more important functions of BK, such as increases in vascular permeability, pain, and vasodilatation, however, are mediated by the B.sub.2 receptor. These effects at the B.sub.2 receptor are believed to be responsible for BK's role in numerous diseases, such as inflammation, cardiovascular disease, pain, and the common cold. Hence antagonists at the B.sub.2 receptor should find considerable therapeutic applications. Most of the efforts in this area thus far have been directed at peptidic analogues of the BK structure, some of which have been studied as analgesics and antiinflammatory agents.
International Publication Number WO 96/06082 discloses a variety of 1,4-dihydropyridine compounds having a piperazinylcarbonylmethy group at the 2-position, as antagonists of bradykinin.
It would be desirable if there were provided a non-peptide antagonist of the B.sub.2 receptor, having an improved B.sub.2 antagonistic activity and a good metabolic stability.